PDF(Pubmed)
Abstract：
BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia.
METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation.
RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression.
CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation.
RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression.
CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
摘要：
背景：高脂血症损害血管壁，是动脉粥样硬化等疾病的基础，高血压和僵硬。NOD样受体家族含pyrin结构域3（NLRP3）炎性体与高脂血症诱导的血管损伤相关的血管功能障碍有关。丹参酮IIA磺酸钠（STS），一种公认的心血管保护药物，具有公认的抗炎作用，抗氧化剂，和血管舒张特性，尚未对其对高脂血症引起的血管松弛剂失衡的影响进行彻底研究。
方法：在本研究中，我们用STS处理ApoE敲除（ApoE-/-）小鼠，并评估NLRP3炎性体的激活，表达MMP2/9，弹性纤维的完整性，血管收缩和松弛。
结果：我们的发现表明，STS干预有效地保留了弹性纤维，显著恢复ApoE-/-小鼠的主动脉舒张功能，并减少他们的过度收缩。此外，STS抑制脾酪氨酸激酶（SYK）的磷酸化，抑制NLRP3炎性体激活，并降低MMP2/9表达。
结论：这些结果表明，STS通过调节SYK-NLRP3炎性体-MMP2/9通路保护血管松弛免受高脂血症诱导的损伤。这项研究为高脂血症环境中血管舒张功能受损的机制提供了新的见解，并揭示了STS保留血管舒张功能的独特机制。为其在促进血管健康方面的临床应用提供有价值的基础研究证据。
方法：在本研究中，我们用STS处理ApoE敲除（ApoE-/-）小鼠，并评估NLRP3炎性体的激活，表达MMP2/9，弹性纤维的完整性，血管收缩和松弛。
结果：我们的发现表明，STS干预有效地保留了弹性纤维，显著恢复ApoE-/-小鼠的主动脉舒张功能，并减少他们的过度收缩。此外，STS抑制脾酪氨酸激酶（SYK）的磷酸化，抑制NLRP3炎性体激活，并降低MMP2/9表达。
结论：这些结果表明，STS通过调节SYK-NLRP3炎性体-MMP2/9通路保护血管松弛免受高脂血症诱导的损伤。这项研究为高脂血症环境中血管舒张功能受损的机制提供了新的见解，并揭示了STS保留血管舒张功能的独特机制。为其在促进血管健康方面的临床应用提供有价值的基础研究证据。
